Peck R, Brockhaus M, Frey J R
F. Hoffmann-LaRoche Ltd., Basel, Switzerland.
Cell Immunol. 1991 Feb;132(2):308-18. doi: 10.1016/0008-8749(91)90030-f.
Several tumor target cell lines, prototypically K562 cells, are resistant to lysis by recombinant tumor necrosis factor (TNF alpha) but are killed by monocytes expressing membrane-associated TNF, suggesting that membrane TNF could account for monocyte-mediated cytotoxicity. Formaldehyde-fixed monocytes or extracted monocyte membrane fragments are cytotoxic to K562 target cells. Treatment of monocytes with interferon-gamma (IFN-gamma) increases cytotoxicity by live and fixed cells or by extracted monocyte membranes. Both TNF and TNF receptors are detectable on monocyte membranes by FACS analysis, and the levels of each are modulated by treatment with IFN-gamma. Cytotoxicity can be inhibited by either anti-TNF or anti-TNF receptor antibodies. Incubation of effector cells with exogenous soluble TNF prior to fixation or membrane preparation increases their cytotoxicity. In contrast, incubation of the target cells with exogenous TNF neither increases nor decreases killing by effector cell membrane fragments or intact effector cells. The data suggest that the TNF receptors on the effector cell, but not on the target cell, play a crucial role in TNF-mediated cytotoxicity.
几种肿瘤靶细胞系，典型的如K562细胞，对重组肿瘤坏死因子（TNFα）介导的裂解具有抗性，但可被表达膜相关TNF的单核细胞杀伤，这表明膜TNF可能是单核细胞介导的细胞毒性的原因。甲醛固定的单核细胞或提取的单核细胞膜片段对K562靶细胞具有细胞毒性。用干扰素-γ（IFN-γ）处理单核细胞可增加活细胞和固定细胞或提取的单核细胞膜的细胞毒性。通过FACS分析可在单核细胞膜上检测到TNF和TNF受体，并且每种的水平都可通过IFN-γ处理进行调节。细胞毒性可被抗TNF或抗TNF受体抗体抑制。在固定或制备膜之前，将效应细胞与外源性可溶性TNF孵育可增加其细胞毒性。相反，将靶细胞与外源性TNF孵育既不会增加也不会降低效应细胞膜片段或完整效应细胞的杀伤作用。数据表明，效应细胞而非靶细胞上的TNF受体在TNF介导的细胞毒性中起关键作用。
